The invention relates to an ophthalmic treatment system and method.
Most ocular treatments require frequent topical administration of drugs to the tissues of the ocular cavity. Further, in situations where there is a deficiency of tears or moisture in the eye, artificial tears must be applied frequently directly to the eye to provide moisture and lubrication.
For both situations, where additional lubrication and moisture are required in the eye, or where medication must be applied topically to the eye, one common form of treatment is the use of liquid drops. The liquid drop form is extremely easy to use as the patient merely self-administers the liquid through an eye dropper or dispenser which includes an eye drop extension end. However, a substantial disadvantage of the liquid form is that the medication or lubricating solution rapidly drains from the ocular cavity into the nasal cavity through an opening called the punctum. The draining liquid may be absorbed by the mucous membrane of the nose and throat causing systemic toxicity which could be minimized by using less drug and fewer administrations and holding the drug in more prolonged contact with the eye. Further, the liquid may simply evaporate from the eye.
Thus, with the use of liquid treatments, a continuous prolonged delivery of lubricant or medication is not achieved, and in the case of drug delivery, the exact dosage is unpredictable as the liquid drains out of the eye. Even with intermittent administration, the liquid treatment will continue to rapidly wash out of the eye, and the continued problem of unpredictability of dosage remains. Further, continuous administration of liquid is not only inconvenient, but may be dangerous.
Several systems shown in U.S. patents provide large ocular inserts to deliver drug to an eye continuously. Certain inserts disperse the drug and require removal of the carrier of the drug once the drug has been delivered. However, U.S. Pat. Nos. 3,845,201; 4,164,559 and 4,179,497 show various inserts in the form of large pellets which dispense drug over a period of time and eventually are completely eroded, and thus do not require removal after drug delivery.
These inserts have certain advantages over the liquid treatments as more predictable dosage is obtained as there is a continuous dispensing of the drug over a period of time without rapid washout. Further, the inserts can be placed directly under the eyelid in the cul-de-sac of the conjunctival sac. Thus, the unitary ocular inserts provide predictable dosage over a period of time without the requirement of repeated applications as required with liquid treatments.
However, there are several disadvantages which accompany the use of unitary ocular inserts. First, as these inserts are fairly large, discomfort or irritation of the sensitive tissues of the eye may occur. Further, the unitary inserts must be carefully placed under the eyelid, and require special care and special insert devices for insertion. Difficulties in patient education in inserting these inserts and compliance with proper technique have prevented their widespread use. Also, as the ocular inserts are rather large and unitary, they are sometimes accidentally ejected from the ocular cavity by the blinking action of the eyelids.
In an attempt to address the problems of liquid treatments and ocular inserts, U.S. Pat. Nos. 3,914,402; 4,001,388 and 4,115,554 all to Shell, show ophthalmic forms which include a suspension of solid particles from 10 to 300 microns in largest dimension in a liquid medium. The Shell dosage form alleviates certain problems associated with ocular inserts, such as complicated insertion, discomfort due to size and the possibility of the insert popping out. However, due to the extremely small size of the solid particles in the suspension of Shell, an extremely important advantage of the ocular inserts is lost, namely the predictability of dosage and continuous dispensing of drug or lubricant.
In all of the Shell patents, it is specifically stated that the solid particles of the suspension are small enough to be passed from the ocular cavity through the punctum. Further, this is evident from the range of the particle size as being from 10 to 300 microns in largest dimension, and the average size of the punctum is about 0.5 mm. Thus, Shell intentionally provides solid particles smaller than the punctum. Shell asserts that the particles of the suspension do not drain from the ocular cavity through the punctum. Although Shell makes this assertion, in practice it cannot be explained why particles smaller in diameter than the punctum would not wash and drain out of the eye in the normal course of drainage provided by the duct system. Further, as the particles in Shell are delivered in a liquid suspension, the excess liquid delivered to the eye would naturally drain through the punctum. As the particles are suspended in this liquid and are specifically smaller than the punctum diameter, it cannot be seen what would prevent the particles from draining out of the eye when delivered with the draining liquid. Thus, although Shell asserts otherwise, the tiny particles in the Shell suspension would not provide a predictable dosage as some of the particles would have to wash out through the punctum with the excess liquid delivered with the Shell system. Although some of the particles in Shell may actually lodge in the soft tissues of the eye, a substantial number of particles will drain out of the eye.
U.S. Pat. No. 3,826,258 to Abraham shows a gradual release medicine carrier. Abraham addresses topical treatment of the eye using capsules which are dropped into the eye. Abraham addresses the problem of irritation or discomfort in the eye by broadly stating that the diameter of the spherical capsules should be less than about 1 millimeter. Abraham does not address a specific size which would not cause irritation in the eye and broadly states a maximum diameter. However, a maximum diameter of about 1 millimeter would be very irritable to the eye.
Further, Abraham does not address the problem of particles draining through the punctum of the eye. Abraham does not suggest a minimum dimension of the capsules to prevent drainage through the punctum. The punctum has an average size of 0.5 millimeters and thus, a large portion of Abraham's broad size range of capsules would drain through the punctum. Abraham in no way addresses the problems of drainage through the punctum and broadly states that the capsule should not be irritable to the eye without really giving any further guidance, of dimensions or consistency which would achieve this single broadly recited purpose related to size.
Further, Abraham in no way discusses balancing of the smallest dimension as opposed to a largest dimension such that concerns of irritation as well as drainage through the punctum are both accounted for. On the contrary, Abraham suggests the use of spherical capsules which presumably would have uniform dimensions. Thus, there is no suggestion in the Abraham patent to create dimensions of the capsule in order to help prevent drainage through the punctum without increasing the possibility of irritation to the eye.
Thus, an object of the present invention is to provide an eye treatment system and method of treatment which provides a continuous administration of the treatment media over a period of time.
It is a further object to provide a treatment system method which delivers a predictable dosage or amount of treatment media to the eye. It is a further object to provide an ophthalmic treatment system easily administered to the eye which will remain in the ocular cavity over a period of time without the risk of premature drainage or popping out of the eye.
It is a further object to provide an ophthalmic treatment system that is prolonged because drainage from the eye through the punctum is prevented, delayed or hindered, and which at the same time is comfortable such that it does not irritate the sensitive eye tissue.
The present invention retains all the advantages of the known treatment systems discussed above, while obviating all of the disadvantages associated therewith.
These and other objects are achieved by providing an ophthalmic treatment system which includes three dimensional particles of bioerodible material being at least 0.5 mm in greatest dimension and being no greater than about 0.4 mm to 0.7 mm in smallest dimension when disposed in the ocular environment. These particles are suspended in a liquid carrier or ointment carrier having a pH acceptable to the eye. In this treatment system, the bioerodible material is released in the eye as the particles erode in response to the ocular environment. Methods for treating the eye are also provided using the system discussed above.
Due to the specific minimum size of the largest particle dimension, the present invention provides optimum prevention of drainage through the punctum, and thus provides optimum prolonged delivery, as well as a predictable dosage that will remain in the eye. It should be noted that this specification is merely a minimum, and it is contemplated that the largest dimension be 4 mm or even greater to maximize the amount of material delivered. At the same time, due to the specific size of the smallest particle dimension in the ocular environment, the treatment system will not be uncomfortable or irritate the eye.
The present invention thus includes the advantages of prior suspensions of particles no greater than 300 microns, as well as liquid treatments in ease of application, no risk in being dislodged from the eye once applied, and minimal irritation or discomfort. However, the present invention also avoids problems associated with prior liquid treatments and suspensions of minute particles which are smaller in size than the punctum, such as the drainage of the treatment in these systems out of the eye through the punctum when applied to the eye.
Further, the present invention includes the advantages of solid inserts such as predictable dosage, and prolonged release of the treatment without drainage through the punctum. However, the present invention also avoids problems associated with solid inserts such as discomfort or irritation of the eye, blurred vision, complicated insertion requiring special skills and equipment, and the risk of being ejected from the eye during blinking.
According to other advantageous features of certain preferred embodiments of the invention, drug is provided in the particles of bioerodible material. Thus, the suspension provides a drug delivery system to the ocular environment.
According to other advantageous features of certain preferred embodiments of the invention, the system serves as an artificial tear treatment. According to certain of these embodiments, the bioerodible material itself provides the artificial tear treatment to the eye when eroded by the ocular environment. Such a system provides proper lubrication and wetting. In certain preferred embodiments, other natural components of the tears are included in the particles or in the solution. Specifically, in certain embodiments, lipid is included in the particles or in the solution.
According to other advantageous features of certain preferred embodiments of the invention, the particles are in a soft, malleable form such that the particles are deformed by the eyelid when placed in the ocular environment between the eyelid and the eye, and are not irritating to the eye if disposed between eyelids. In further preferred embodiments, the particles can be in a semi-solid form and thus are malleable and provide comfort to the eye. In certain embodiments, the size of the smallest dimension is greater than the preferred range prior to administration, and are compressed to the preferred range when administered to the eye. The malleable form or consistency provides a soft contact to the eye tissue and forms rounded edges, thereby further enhancing comfort.
Methods of treatment corresponding to the various preferred embodiments are also provided.
Other objects, advantages and novel features of the present invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings.